Treatment of metastases at the secondary sites is limited by possible involvement of a large volume of critical normal tissues. Prevention and control of metastases at the early phase of the metastatic processes would be highly desirable. Additionally, recent results from our continued experimentation on metastases indicate that tumor-cell-release is a critical step in spontaneous metastasis. Our newly developed methods directly measure "clonogenic" blood-borne tumor cells and "clonogenic" tumor cells trapped at the lung. Using these techniques we would like: 1) to test generality of a hypothesis that "clonogenic" blood-borne tumor cells (or tumor-cell-release processes) are important in metastasis (Specific Aims 1, 2). 2) to determine feasibility of "clonogenic" tumor-cell-release (CTCR) processes and newly released lung-trapped tumor cells as targets for prevention and control of metastasis by radiation with or without hyperthermia (Specific Aims 3, 5, 6). 3) to determine behavior of clonogenic tumor cells in the lung, i.e., characteristics of initial trapping-retention-growth of clonogenic tumor cells after i.v. injection. Our hypothesis is that tumor-cell-killing at the lung is slow and random in nature and not selective (Specific Aims 4, 6). 4) to determine host defense mechanism(s) at the lung (type of cells involved) and effect of thorax (lung) irradiation on them (Specific Aims 4, 6). We believe that these studies will provide a better understanding of metastasis (specifically, CTCR processes, newly released tumor cells and host defense at the lung) and eventually provide rationale(s) to develop better methods for prevention and control of metastatic spread in patients.